Introduction
The genomic landscape of Langerhans cell histiocytosis (LCH) has been markedly transformed by the identification of variants activating the mitogen-activated protein kinase (MAPK) pathway, the first and most common being the BRAF p.V600E mutation. 1In-frame BRAF deletions have subsequently been found in LCH, the most common being the BRAF p.N486_P490 deletion, which was recently detected in 19 of 69 (28%) of adults with LCH evaluated by next generation sequencing (NGS). 2 MAPK pathway inhibition resulted in remarkable responses, but with rapid reactivation upon discontinuation of therapy. 3,4 Trametinib, a MEK1/2 inhibitor, showed impressive activity in an adult patient reported by Lee et al. 5 Yet, acquired resistance to trametinib due to MAP2K1 mutations were also recently reported.6 Here we are reporting 3 LCH patients withBRAF p.N486_P490del or MAP2K1 p.K57_G61del who are responding to trametinib monotherapy.